Targeted DNA demethylation of the ZNF334 promoter inhibits colorectal cancer growth

Abstract

Colorectal cancer (CRC) is a leading cause of cancer deaths worldwide. Aberrant regulation of DNA methylation in promoters of tumor suppressor genes or proto-oncogenes is one of the fundamental processes driving the initiation and progression of CRC. Zinc-finger proteins (ZNFs) are one of the most abundant groups of proteins and function in many important biological processes related to tumorigenesis. Herein, we detected abnormal hypermethylation of the ZNF334 gene in CRC tissues compared with normal tissues, and this modification downregulated the expression of ZNF334. Furthermore, ten-eleven translocation 1 (TET1) was identified to be involved in regulating the methylation level of ZNF334. Next, a dCas9-multiGCN4/scFv-TET1CD-sgZNF334-targeted demethylation system was constructed to reverse the expression of ZNF334 through sgRNA targeting the ZNF334 promoter. Both in vitro and in vivo experiments demonstrated the targeted demethylation system upregulated ZNF334 expression and inhibited CRC growth. Collectively, targeted DNA demethylation of the ZNF334 promoter sheds light on the precise treatment of CRC.

Functional impact of multi-omic interactions in lung cancer

“…FLT3 has been identified as being overexpressed in hematologic malignancies, such as acute myelogenous leukemia ( Gilliland and Griffin, 2002 ). On the other hand, upregulation of ZNF334 has been associated with hepatocellular carcinoma (HCC), and triple-negative breast cancer (TNBC) ( Yang et al, 2023 ). This limited association suggests that it is necessary to do an exhaustive research in FLT3 and ZNF334 properties related to NSCLC and re-evaluate its impact in the disease development.…”

Implications of ZNF334 gene in lymph node metastasis of lung SCC: potential bypassing of cellular senescence

“…ZNF334 is a newly identified member of Zinc Finger Proteins (ZNFs), and over the last few decades, increasing evidence has supported key roles for ZNFs in cancer metastasis through regulating transcription of downstream genes, which are involved in proliferation, apoptosis, senescence, migration, and invasion [ 40 ]. The second selected down-regulated gene is TINAGL1 , an extracellular matrix protein that promotes integrin-mediated cell adhesion, whose expression is dependent on Sec.…”

“…Cheng et al reported decreased expression of ZNF334 in breast cancer tissues and cell lines and showed that re-expression of ZNF334 in TNBC cell lines could suppress their growth and metastatic capacity [ 42 ]. Yang et al detected the downregulation of ZNF334 gene expression in the occurrence of colorectal cancer and defined it as a molecular marker for the early diagnosis of colorectal cancer [ 40 ]. Similarly, Sun et al clarified the effect of the ZNF334 deletion on the occurrence of hepatocellular carcinoma and described it as a molecular marker for liver cancer early diagnosis [ 43 ].…”